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The metabolic sensor LKB1 regulates ILC3 homeostasis and mitochondrial function.
Diogo Fonseca-Pereira1, Sena Bae1, Slater L Clay1
1Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Harvard T.H. Chan Microbiome in Public Health Center, Boston, MA, USA.
Cell Reports
|March 22, 2025
Summary
Liver kinase B1 (LKB1) is essential for group 3 innate lymphoid cells (ILC3s) to maintain gut immunity. LKB1 controls ILC3 survival, cytokine production, and mitochondrial function, impacting tissue homeostasis.
Area of Science:
- Immunology
- Cell Biology
- Metabolism
Background:
- Group 3 innate lymphoid cells (ILC3s) are critical for mucosal immunity and tissue homeostasis.
- Liver kinase B1 (LKB1) is a key metabolic sensor regulating immune cell function.
- The specific role of LKB1 in ILC3s remained uncharacterized.
Purpose of the Study:
- To investigate the function of LKB1 in adult ILC3 homeostasis and effector functions.
- To elucidate the molecular mechanisms by which LKB1 regulates ILC3s.
Main Methods:
- Conditional deletion of LKB1 in ILC3s.
- Analysis of ILC3 numbers, survival, and cytokine production (IL-22).
- Assessment of mitochondrial function, bioenergetics, and signaling pathways (MARKs, ROS, NFAT2, PD-1).
Main Results:
- LKB1 deletion in ILC3s led to reduced cell numbers and impaired IL-22 production.
- LKB1-deficient ILC3s exhibited mitochondrial dysfunction, reduced survival, and altered bioenergetics.
- LKB1's regulation of ILC3s requires MARK signaling and impacts ROS, NFAT2, and PD-1 expression.
Conclusions:
- LKB1 is crucial for maintaining adult ILC3 homeostasis, survival, and IL-22 production.
- LKB1-dependent metabolic regulation is vital for intestinal immunity and tissue homeostasis via ILC3 function.
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